Nonsteroidal antiinflammatory drugs and the lupus anticoagulant

Abstract

Table 1. Laboratory findings in patient I . who was receiving continuous ambulatory peritoneal dialysis, after treatment with a single dose of oral methotrexate followed by leucovorin rescue. Serum MTX WBC, level. Hgb. x 10'/mm' Platelets. Date Drug pmolesniter gm/dl (% segments) x IO'lmm' 3/2/89 3/6/89t 3/8/89 3/9/89$ 31 I0/89+ 311 4/89 3/16/89 3120189 2.5 mg MTX -0.12 10.7 9.2 (81) 323 270 75 mg leucovorin 0.09 11.0 75 mg leucovorin 0.13 ND 1.8 (61) ND 75 mg leucovorin 0.10 10.0 0.8 (15) I50 75 mg leucovorin 0.02 7.0 0.5 (24) 99 -ND 6. I 3.1 (30) 35 co.01 9.0 10.0 (27) 71 2.0 (SO) * Serum methotrexate (MTX) levels were determined by fluorescence polarization on a TDX, using Abbott reagents (Abbott Laboratories. North Chicago. IL). Hgb = hemoglobin; WBC = white blood cells; ND = not determined. t Date of hospital admission. $ Charcoal hemoperfusion was performed. leucovorin or hemoperfusion. She was continued on her regimen of hemodialysis 3 times a week, with antibiotic use and standard isolation techniques. Her PM improved and CPK levels normalized without additional treatment and have remained constant for more than 5 months post-MTX administration.The final decision to use MTX in the 2 patients described was made only after a lengthy discussion with colleagues and a review of the report by Janknegt et al(1). It was our impression that, under extenuating circumstances. other rheumatologists are using or might consider using MTX in patients similar to the 2 described here. However. this report documents the catastrophic events we encountered. Oral administration of MTX in renal dialysis patients seems equivalent to continuous infusion of the drug, since there are few effective means for removing MTX from body fluids without adequate renal function. MTX is poorly cleared with hernodialysis and cleared even less with peritoneal dialysis (5). Cholestyramine administration was not used in our patients but may be of some value in providing nonrenal clearance of MTX (3,4). Measurements of MTX levels and earlier leucovorin administration might have helped our first patient, but our overall experience with both patients has convinced us that MTX cannot be used safely in renal dialysis patients. I . Janknegt R, Nube MI. van den Hoogenband HM. Oldenhof HGJ. Steenhoek A. Vree TB: Pharmacokinetics of methotrexate in continuous ambulatory peritoneal dialysis. Pharm Weekbl [Sci] 10:8689, 1988 2. Steinberg SE, Campbell CL, Bleyer WA. Hillman RS: Enterohepatic circulation of methotrexate in rats in vitro. Cancer Res 42:127%1282, 1982 3. Erttmann R, Landbeck G : Effect of oral cholestyramine on the elimination of high-dose methotrexate. J Cancer Res Clin Oncol I10:48-50, 1985 4. Nurnberg B. Jacobi A. Faulkner R, Koehnke R. Hoffman I. Furst D: Biliary elimination of low dose methotrexate in man (abstract). Arthritis Rheum 31 (suppl 4):S116. 1988 5. Thierry FX. Vernier I . Dueymes JM. Roche H, Canal P. Meeus F. Pourrat JP, Conte JJ: Acute renal failure after high-dose methotrexate therapy (letter). Nephron 51:416417, 1989 Nonste...